Acute stroke is a common and devastating disorder, the 3rd leading cause of death and leading cause of adult disability in the US. This application for renewal of the UCLA Specialized Program of Translational Research in Acute Stroke Center proposes an integrated research/training program to develop innovative therapies for acute ischemic and hemorrhagic stroke. Five research projects are proposed. Project 1, the Therapeutic Aqueous Oxygen (TAO) Trial is a 50 patient trial to evaluate the feasibility and safety of endovascular delivery of supersaturated, aqueous oxygen to ischemic human cerebral tissues. This trial will be the first formal study of endovascular infusion of neuroprotective agents, a highly promising complementary strategy to endovascular recanalization. Project 2, the Intraoperative CT and Endovascular-Guided Surgery for Intracerebral Hemorrhage (ICES) Trial is a critical phase 2 trial of a new, minimally invasive surgical technique for the evacuation of primary intracerebral hemorrhage, using mobile intra-operative CT and neuroendoscopy. In addition, studies interrogating the fundamental pathophysiology of brain injury in human ICH are proposed delineating differential gene expression, tissue morphometrics, and multimodal MR signatures in the perihematomal region. In Project 3, Telestroke in the Field: Improving Prehospital Stroke Care with Mobile Broadband Telemedicine Technologies, will evaluate the benefit upon prehospital diagnostic accuracy and informed consent of physician-patient interaction in the field employing emerging video handset technologies. Project 4, The MR and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) Trial, is an international, multicenter pilot trial to determine whether diffusion-perfusion MRI can identify acute cerebral ischemia patients who will benefit substantially from mechanical embolectomy with the Merci Retriever up to 8 hrs from symptom onset. Project 5, the Counterpulsation to Upgrade Forward Flow in Stroke (CUFFS) Trial will assess the tolerability, feasibility, and safety of increasing blood flow to ischemic cerebral fields through external counterpulsation in 30 patients with persisting arterial occlusion. Five Cores support the Projects: Administrative, Patient Access, Blood/Tissue Specimen, Biostatistics/Data Management, and Neuroimaging. A Career Development Program will train the next generation of translational scientists in neurovascular disease at the premedical, medical student, and fellowship level.